What are the possible diagnoses for a patient with hyperaldosteronism and elevated renin levels, presenting with hypertension?

Differential Diagnosis: Elevated Renin and Aldosterone with Hypertension

Primary Diagnosis to Consider

Secondary hyperaldosteronism is the most likely diagnosis when both renin (337 mU/L) and aldosterone (10 ng/dL) are elevated together with hypertension. 1, 2

Key Diagnostic Distinction

The critical finding here is that both renin AND aldosterone are elevated, which fundamentally distinguishes this from primary aldosteronism where renin would be suppressed (typically <0.5-1.0 ng/mL/hr) despite elevated aldosterone. 1, 2, 3

Calculate the Aldosterone-to-Renin Ratio (ARR)

• With aldosterone at 10 ng/dL and markedly elevated renin at 337 mU/L (approximately 6.7 ng/mL/hr if converting from mU/L), the ARR would be approximately 1.5, which is well below the screening threshold of 20-30 for primary aldosteronism. 1, 3
• This low ARR effectively rules out primary aldosteronism as the cause. 2, 3

Differential Diagnoses to Consider

1. Renovascular Hypertension (Most Likely)

• Renal artery stenosis from atherosclerosis or fibromuscular dysplasia causes appropriate activation of the renin-angiotensin-aldosterone system, leading to elevated renin with secondary aldosterone elevation. 1, 2
• Clinical indicators include: resistant hypertension, abrupt onset or worsening hypertension, flash pulmonary edema (atherosclerotic), early-onset hypertension especially in women (fibromuscular dysplasia), abdominal systolic-diastolic bruit. 1
• Screening tests: Renal Duplex Doppler ultrasound, MRA, or abdominal CT angiography. 1
• Confirmatory test: Bilateral selective renal intra-arterial angiography. 1

2. Renal Parenchymal Disease

• Chronic kidney disease activates the renin-angiotensin system appropriately, causing secondary hyperaldosteronism. 1, 2
• Clinical indicators include: urinary tract infections, obstruction, hematuria, urinary frequency and nocturia, analgesic abuse, family history of polycystic kidney disease, elevated serum creatinine, abnormal urinalysis. 1
• Screening tests: Plasma creatinine, sodium, potassium, eGFR, urine dipstick for blood and protein, urinary albumin-to-creatinine ratio, renal ultrasound. 1

3. Diuretic Use or Volume Depletion

• Diuretics, particularly loop and thiazide diuretics, cause volume depletion that appropriately stimulates renin release, leading to secondary aldosterone elevation. 1, 2
• Both renin and aldosterone increase together (↑↑ for both), which can create a false negative ARR for primary aldosteronism screening. 1
• Key action: Review medication history for potassium-wasting diuretics. 1

4. Medications Affecting the Renin-Angiotensin System

• ACE inhibitors and ARBs cause marked elevation in renin (↑↑) while decreasing aldosterone (↓), typically lowering the ARR and creating false negatives. 1
• However, if the patient has been recently started on these medications or has underlying renovascular disease, both values could be elevated. 1, 2
• Review current medications including ACE inhibitors, ARBs, calcium channel blockers, and diuretics. 1

5. Primary Aldosteronism with Secondary Hypertensive Kidney Damage (Rare)

• In severe, longstanding primary aldosteronism with hypertensive kidney damage, renin can "escape" from suppression due to renal arteriolosclerosis. 4
• These patients still have a disproportionately elevated ARR (typically still >20-30) because aldosterone remains inappropriately high relative to renin. 4
• All three reported cases had high-normal or slightly elevated serum creatinine and histologically proven renal arteriolosclerosis. 4
• This is an uncommon presentation but should be considered if ARR is borderline elevated (>20) despite non-suppressed renin. 4

Diagnostic Algorithm

Step 1: Medication Review

• Identify and document all antihypertensive medications, particularly diuretics, ACE inhibitors, ARBs, and beta-blockers. 1
• Consider withdrawing interfering medications when clinically feasible: stop beta-blockers, centrally acting drugs, and diuretics; use long-acting calcium channel blockers or alpha-receptor antagonists as alternatives. 1, 3

Step 2: Assess for Renovascular Disease

• Perform renal Duplex Doppler ultrasound as initial screening. 1
• If positive or high clinical suspicion, proceed to MRA or CT angiography of renal arteries. 1
• Look for clinical clues: abdominal bruit, age >60 years with acute BP change, flash pulmonary edema, or age <40 years (fibromuscular dysplasia). 1

Step 3: Evaluate Renal Function

• Measure serum creatinine, eGFR, electrolytes, urinalysis with microscopy, and urinary albumin-to-creatinine ratio. 1
• Perform renal ultrasound to assess for structural abnormalities, obstruction, or polycystic kidney disease. 1

Step 4: Repeat ARR Under Standardized Conditions (If Initial Screening Inconclusive)

• Ensure patient is potassium-replete (correct hypokalemia first). 3
• Collect blood in the morning after patient has been out of bed for 2 hours and seated for 5-15 minutes. 3
• Ensure unrestricted salt intake and normal serum potassium levels. 1, 3
• If ARR remains <20 with both values elevated, secondary hyperaldosteronism is confirmed. 2, 3

Critical Pitfalls to Avoid

• Do not assume primary aldosteronism based on elevated aldosterone alone—the suppressed renin is the defining feature of primary aldosteronism, and this patient has elevated renin. 1, 2
• Do not overlook renovascular disease—it is the most common cause of secondary hyperaldosteronism with this laboratory pattern and is potentially curable with revascularization in fibromuscular dysplasia. 1
• Do not ignore medication effects—diuretics and ACE inhibitors/ARBs can create this exact laboratory pattern and should be withdrawn when feasible before definitive testing. 1, 3
• Do not rely on hypokalemia—it is absent in 50% of primary aldosteronism cases and is not a reliable screening criterion. 1, 5, 2